Chemically induced hepatocarcinogenesis is accompanied by the emergence of new cell populations exhibiting defective control of cellular proliferation and positional order, a phenotypic expression that presumably involves qualitative or quantitative alterations of cell-surface macromolecules, including the plasma membrane glycoproteins. The objective of this research is to delineate the molecular basis of qualitative differences in the plasma membrane glycoproteins of normal and malignant rat liver cells, focusing on alterations in their composition, structure, topography and dynamics. Cell populations to be studied include hepatocytes, primary and transplantable hepatocellular carcinomas and focal, proliferative lesions associated with hepatocarcinogenesis. Hepatocarcinogenesis in the ACI rat, induced by 2-acetylaminofluorene and diethylnitrosamine, will be used as the experimental model. Cells will be radiolabeled using methods specific for cell-surface glycoconjugates, e.g., oxidation with NaIO4 or D-Gal oxidase followed by reduction with NaB3H4, procedures that label sialic acids and D-Gal/D-GalNAc residues, respectively. Radiolabeled glycoproteins will be solubilized with nonionic detergent (Nonidet P-40) and resolved by polyacrylamide gel electrophoresis and affinity chromatography using carrier bound lectins. The major plasma membrane glycoproteins will be characterized with regard to their extractability from the membrane, liability to protease, primary structure as determined by mapping of tryptic peptides, and immunological cross-reactivity. Immunocytochemical techniques, using monoclonal antibodies prepared against selected glycoproteins, will be employed to assess the topographic and dynamic aspects of the integration of glycoproteins into the plasma membrane. Qualitative alterations of the plasma membrane glycoproteins will be correlated with the carcinogenic process, malignant transformation and selective processes involved in tumor progression.